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This longitudinal study explored the intricate relationships between serum Brain-Derived Neurotrophic Factor (sBDNF) levels, exposure to childhood adversities, and the subsequent development of Post-Traumatic Stress Disorder (PTSD), distinguishing between earlier- and delayed-onset forms over a two-year follow-up period in individuals sustaining physical injuries. We recruited patients presenting with moderate to severe physical injuries at a trauma center, conducting baseline assessments of sBDNF levels and childhood adversities through the Adverse Childhood Experiences (ACE) questionnaire. Additionally, detailed socio-demographic and clinical data were compiled. The Clinician-Administered PTSD Scale for DSM-5 was employed to diagnose PTSD at 3, 6, 12, and 24 months post-injury. Binary and multinomial logistic regression analyses were applied to elucidate the interactions between sBDNF levels, childhood adversities, and PTSD onset patterns. Among 895 participants, PTSD was diagnosed in 107 individuals (11.9 %), with 76 (8.4 %) exhibiting symptoms indicative of earlier-onset PTSD and 31 (3.5 %) demonstrating delayed-onset PTSD. Significantly, lower sBDNF levels were associated with a higher risk of earlier-onset PTSD specifically in the context of childhood adversities. This association was not observed in individuals without childhood adversities or in those with delayed-onset PTSD. The findings suggest a complex and critical interplay between neurobiological factors, specifically sBDNF levels, and early life adversities in influencing the timing of PTSD onset, potentially deepening the understanding of PTSD etiology., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biotin is an essential coenzyme involved in various metabolic processes across all known organisms, with biotinylation being crucial for the activity of carboxylases. BirA from Haemophilus influenzae is a bifunctional protein that acts as a biotin protein ligase and a transcriptional repressor. This study reveals the crystal structures of Hin BirA in both its apo- and holo-(biotinyl-5'-AMP bound) forms. As a class II BirA, it consists of three domains: N-terminal DNA binding domain, central catalytic domain, and C-terminal SH3-like domain. The structural analysis shows that the biotin-binding loop forms an ordered structure upon biotinyl-5'-AMP binding. This facilitates its interaction with the ligand and promotes protein dimerization. Comparative studies with other BirA homologs from different organisms indicate that the residues responsible for binding biotinyl-5'-AMP are highly conserved. This study also utilized AlphaFold2 to model the potential heterodimeric interaction between Hin BirA and biotin carboxyl carrier protein, thereby providing insights into the structural basis for biotinylation. These findings enhance our understanding of the structural and functional characteristics of Hin BirA, highlighting its potential as a target for novel antibiotics that disrupt the bacterial biotin synthesis pathways., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Endoscopic carpal tunnel release (ECTR) has advantages over open carpal tunnel release (OCTR); however, complications with ECTR are more likely to occur if the surgeon continues the procedure despite encountering difficulties. Techniques to minimize the need for conversion to OCTR have been infrequently discussed in the literature. This study aims to present a technique for performing ECTR without conversion to the open approach and to analyze the reasons for such conversions., Methods: A total of 1160 hands in 771 patients who underwent single-portal ECTR between January 2001 and December 2020 were analyzed. We evaluated the rate and reasons for conversion and compared clinical severity and electrodiagnostic grades between the ECTR and OCTR conversion groups to identify patient characteristics associated with conversion., Results: A total of 18 hands in 17 patients required conversion to OCTR (1.56%). In the first 5 years, 9 out of 251 ECTRs (3.59%) were converted, but since then, the conversion rate significantly decreased with increasing surgical experience. The most common reasons for conversion were poor visualization of the transverse carpal ligament due to the transbursal approach with a hypertrophic synovial membrane. As the preoperative clinical grade worsened, the conversion rate significantly increased. The OCTR conversion rate also tended to rise with more severe electrodiagnostic grades. Outcomes for all 18 wrists were successful at the 6-month follow-up., Conclusions: A thorough subligamentous extrabursal approach is essential for achieving a clear endoscopic view of the transverse carpal ligament and performing ECTR without the need for conversion to open surgery., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: During the height of the recent Coronavirus (COVID-19) pandemic, several surgeries were transitioned to ambulatory surgery centers to reserve inpatient resources and reduce transmission risks. Our study evaluated the surgical outcomes of patients who underwent prepectoral breast reconstruction in the operating rooms of two full-service main hospitals versus their associated surgery centers., Methods: A retrospective chart review was conducted of patients who underwent immediate prepectoral breast reconstruction at a single hospital between 2018 and 2022. Eligible patients had at least 3 months of post-expander follow-up, with the majority also having 3 months of post-implant follow-up. Patient demographics, reconstructive characteristics, post-expander outcomes, and post-implant outcomes were evaluated between the surgery center and main operating room using the chi-squared (or Fisher's exact) and Wilcoxon ranked-sum tests., Results: This study included 301 patients, outcomes of 509 post-expander breasts, and outcomes of 410 post-implant breasts. The patient characteristics were similar with the only significant difference being the hospital length of stay (increased stay at the main hospital). There were no statistically significant differences in any of the surgical outcomes between the two groups in the post-expander or post-implant period., Conclusion: The COVID-19 pandemic disrupted elective procedures, prompting a shift toward outpatient surgery to optimize hospital resources and reduce inpatient exposure risks. Although breast reconstruction is elective, delays can pose risks for patients with cancer. Our results show that surgical outcomes for prepectoral prosthetic breast reconstruction remain consistent whether performed in outpatient surgical centers or main hospitals., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Oropharyngeal dysphagia (dysphagia) is highly prevalent (up to 86%) in hospitalized patients with Alzheimer disease and related dementias (ADRD). This study aims to describe the management and clinical course of dysphagia in hospitalized patients with ADRD., Design: Prospective observational cohort study., Setting and Participants: The study was conducted across 10 hospitals within a large health system in New York. Participants were older adults with ADRD admitted to the medicine service and diagnosed with dysphagia to liquids on speech-language pathologist (SLP) assessment and were recruited between January and June 2023., Methods: Baseline characteristics [eg, dementia Functional Assessment Staging Tool (FAST)], dysphagia management (eg, prescribed diet), and clinical course (eg, dysphagia improvement, respiratory complications) were collected., Results: Of patients with ADRD and dysphagia (n = 62), the average age was 86.5 and 66.1% were FAST Stage 7. On admission, 48.4% had pneumonia, 79.0% had delirium, and 69.4% were made nil per os (NPO) for aspiration risk. Of those who received SLP reassessment after diet initiation (n = 25), 76% demonstrated dysphagia improvement; 75% of patients with FAST stage 7 demonstrated improvement. Respiratory complications occurred in 21.0% of patients on the following diets: NPO, nasogastric tube feeding, dysphagia diets, and comfort feeds. In univariate analyses, hospital-acquired dehydration, no dysphagia improvement, and delirium were associated with respiratory complications., Conclusions and Implications: The potential for dysphagia improvement in hospitalized patients with ADRD (even those with advanced dementia) highlights the critical need for standardizing reassessment. Further studies are needed to evaluate factors associated with respiratory complications in this population., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

This study advances the automation of Parkinson's disease (PD) diagnosis by analyzing speech characteristics, leveraging a comprehensive approach that integrates a voting-based machine learning model. Given the growing prevalence of PD, especially among the elderly population, continuous and efficient diagnosis is of paramount importance. Conventional monitoring methods suffer from limitations related to time, cost, and accessibility, underscoring the need for the development of automated diagnostic tools. In this paper, we present a robust model for classifying speech patterns in Korean PD patients, addressing a significant research gap. Our model employs straightforward preprocessing techniques and a voting-based machine learning approach, demonstrating superior performance, particularly when training data is limited. Furthermore, we emphasize the effectiveness of the eGeMAPSv2 feature set in PD analysis and introduce new features that substantially enhance classification accuracy. The proposed model, achieving an accuracy of 84.73 % and an area under the ROC (AUC) score of 92.18 % on a dataset comprising 100 Korean PD patients and 100 healthy controls, offers a practical solution for automated diagnosis applications, such as smartphone apps. Future research endeavors will concentrate on enhancing the model's performance and delving deeper into the relationship between high-importance features and PD., Competing Interests: Declaration of competing interest We, the authors of the manuscript titled "Machine Learning-Based Classification of Parkinson's Disease Using Acoustic Features: Insights from Multilingual Speech Tasks," declare that we have no conflicts of interest or financial interests that could be construed as influencing the research presented in this paper. We confirm that the research presented in this manuscript was conducted impartially, and we have not received any financial support or incentives that might create a conflict of interest with the results and conclusions of this research. Our primary aim is to contribute to the field of Parkinson's disease diagnosis using machine learning and acoustic features, and we have adhered to ethical standards and best practices throughout the research process. If, in the future, any potential conflicts of interest arise related to this work, we commit to promptly disclosing them to the relevant parties. We have submitted this manuscript to "Computers in Biology and Medicine" with the understanding that the information provided in this Declaration of Interest Statement accurately represents our current affiliations and interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aims to evaluate the effectiveness of a self-management program using gain/loss-framed messages in patients with gastric cancer., Methods: In this randomized controlled trial, 69 patients with gastric cancer who underwent gastrectomy at a university hospital were assigned to the gain- or loss-framed message group. The self-management program consisted of: 1) face-to-face education, 2) gain/loss-framed text messages, and 3) self-monitoring of health behaviors. Health outcomes (i.e., nutritional status, physical activity, exercise intensity, and distress), and health behaviors (i.e., dietary habits, physical activity performance, and distress management) were measured, and a generalized estimating equation was used for the analysis., Results: Nutritional status and dietary habits in the loss framed message group were statistically higher after the intervention compared to the counterpart (β = -1.72, p = .049; β = 0.36, p = .033, respectively). There was no time-group interaction effect on physical activity, exercise intensity, physical activity performance, distress or distress management., Conclusions: A self-management program employing loss-framed messages was effective in promoting nutrition-related self-management among patients with gastric cancer., Practice Implications: Message-framing is an effective communication technique that can be easily used in clinical settings, and a loss-message-framing strategy may enhance nutrition-related self-management in patients with gastric cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The endoscopic combined transseptal-transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach., Methods: Using a retrospective cohort from a pre-eminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal-transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center test, Cross-Cultural Smell Identification Test, Sino-Nasal Outcome Test-22, and nasal obstruction symptom evaluation., Results: The transseptal-transnasal approach exhibited reduced rates of postoperative ear fullness (P < 0.001), along with fewer subjective complaints of smell/taste loss (P = 0.022) and thick nasal discharge (P = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the 2 approaches (P = 0.243 and P = 0.454 for Connecticut Chemosensory Clinical Research Center and Cross-Cultural Smell Identification Test, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal-transnasal approach (P = 0.067)., Conclusions: For the surgical treatment of pituitary adenomas, the transseptal-transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microplastic (MP) pollution in urban environments is a pervasive and complex problem with significant environmental and human health implications. Although studies have been conducted on MP pollution in urban environments, there are still research gaps in understanding the exact sources, regulation, and impact of urban MP on the environment and public health. Therefore, the goal of this study is to provide a comprehensive overview of the complex pathways, harmful effects, and regulatory efforts of urban MP pollution. It discusses the research challenges and suggests future directions for addressing MPs related to environmental issues in urban settings. In this study, original research papers published from 2010 to 2024 across ten database categories, including PubMed, Google Scholar, Scopus, and Web of Science, were selected and reviewed to improve our understanding of urban MP pollution. The analysis revealed multifaceted sources of MPs, including surface runoff, wastewater discharge, atmospheric deposition, and biological interactions, which contribute to the contamination of aquatic and terrestrial ecosystems. MPs pose a threat to marine and terrestrial life, freshwater organisms, soil health, plant communities, and human health through ingestion, inhalation, and dermal exposure. Current regulatory measures for MP pollution include improved waste management, upgraded wastewater treatment, stormwater management, product innovation, public awareness campaigns, and community engagement. Despite these regulatory measures, several challenges such as; the absence of standardized MPs testing methods, MPs enter into the environment through a multitude of sources and pathways, countries struggle in balancing trade interests with environmental concerns have hindered effective policy implementation and enforcement. Addressing MP pollution in urban environments is essential for preserving ecosystems, safeguarding public health, and advancing sustainable development. Interdisciplinary collaboration, innovative research, stringent regulations, and public participation are vital for mitigating this critical issue and ensuring a cleaner and healthier future for urban environments and the planet., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Investigating microplastics (MPs) in groundwater suffers from problems already faced by surface water research, such as the absence of common protocols for sampling and analysis. While the use of plastic instruments during the collection, processing, and analysis of water samples is usually avoided in order to minimize unintentional contamination, groundwater research encompassing MPs faces unique challenges. Groundwater sampling typically relies on pre-existing monitoring wells (MWs) and water wells (WWs) that are often constructed with polyvinyl chloride (PVC) casings or pipes due to their favorable price-performance ratio. Despite the convenience, however, the suitability of PVC casings for MP research is questionable. Unfortunately, the specifics of these wells are often not detailed in published studies. Current literature does not indicate significant pollution risks from PVC casings, suggesting these wells might still be viable for MP studies. Our preliminary analysis of the existing literature indicates that if PVC exceeds 6 % of the total MP concentration, it is likely that casings and pipes made of PVC are a source of pollution. Above this threshold, additional investigations in MWs and WWs with PVC casings and pipes are suggested., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study., Methods: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AA, JC, LR, AJPdSG, FCM, LH, HA, J-YL, VS, FZ, LG, JS, ET, KL, NC, C-LC, MB, HZ, AO, MC, EP, TU, SP, and LRD received funding to their institutions from Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD) to support the study. DL reports grants or contracts from AstraZeneca, Clovis Oncology, Pharma&, Genmab, GSK, Immunogen, MSD, Pharmamar, Novartis, Seagen, Alkermes, Incyte, Roche, and Corcept; consulting fees from AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, and Sutro; speaker fees from AstraZeneca, Corcept, Genmab, GSK, Immunogen, MSD, and Seagen; travel grants from AstraZeneca, Menarini, GSK, and MSD; advisory board participation for AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, and Sutro; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG, MITO, and ENGOT. YX reports study funding, paid to the Peking Union Medical College Hospital, and support for attending meetings or travel from MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, Sanofi, GSK, and Zymeworks; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, Kaken, and GSK; and travel support from Regeneron and Seagen. GS reports consulting fees from AstraZeneca, MSD, Coviden AG (a Medtronic company), Johnson & Johnson, and TESARO Bio Italy; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Baxter Healthcare, Olympus Europa, Intuitive Surgical, GSK, and Clovis Oncology Italy. ML reports payment for expert testimony from MSD, support for attending meetings or travel from MSD and AstraZeneca; and other financial or non-financial interests from MSD, AstraZeneca, and Roche. PR-E reports honoraria for educational events from MSD, AstraZeneca, Novartis, Asofarma, Pfizer, and Roche; support for attending ESMO and ASCO meetings from AstraZeneca, Pfizer, and Asofarma; and honoraria for advisory boards from MSD, Roche, AstraZeneca, Asofarma, BMS and Novartis. LR reports medical writing support from Merck, institutional grants from Merck, Zentalis, Karyopharn, GOG Foundation, Regeneron, ImmunoGen, Acrivon, CanariaBio, Corcept Therapeutics, and Seagen; consulting fees from AstraZeneca, Merck, GSK, Genmab, Seagen, GOG Foundation, Zentalis, ImmunoGen, Semline, Eisai, Caris, Nykode, and Clovis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Seagen and Genmab; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from GOG Foundation. AJPdSG reports consulting fees and payment for expert testimony from Bayer, Astellas, and Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for expert testimony from Astellas, AstraZeneca, Bayer, and Janssen; and participation on a data safety monitoring board or advisory board for Astellas, Bayer, and Janssen. FCM reports honoraria for presentations from MSD and BMS; support for attending meetings or travel from AstraZeneca and MSD; and advisory board participation from Janssen and MSD. J-YL reports support for the present manuscript from MSD; grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Kelun, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and ONO; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for AstraZeneca, CanariaBio, Genmab, GII, ImmunoGen, Seagen, Merck, Sutro, Regeneron, and MSD. FZ reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, consulting fees, support for attending meetings or travel, and data safety monitoring board and advisory board participation for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, MSD, Pfizer, Genesis-Pharma, and Roche. LG reports institutional grants from IMV, Pfizer, Sutro Bio, Pharma, Merck Sharpe Dohme, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group, Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure, Alkermes, Espersas, and Mersana; consulting fees from Merck and GSK; payment or honoraria for lectures and presentations from Merck and GSK; support for attending meetings or travel from GSK, Merck, EndomERA, and Zentalis; and participation on advisory board meetings for GSK, Merck, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, Canariabio, and Repare Therapeutics. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, BMS, Eisai, and Novartis; support for attending meetings or travel from GSK, Astra Zeneca, Roche, Novocure, Immunogen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO; and medical writing assistance from MSD. ET reports honoraria for presentations and meeting travel support from Elektra. KL reports study funding from MSD; grants or contracts from GSK; lecture honoraria from Eisai and AstraZeneca; participation on a data safety monitoring board for Karyopharm; participation on an advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK; and serving as deputy medical director for the Nordic Society of Gynecological Oncology Clinical Trial Unit. NC reports institutional grants from AstraZeneca and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK and MSD; payment for participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD, Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche, and Novocure; and non-remunerated leadership role as Chair of the Alleanza Contro il Tumore Ovarico Scientific Committee. MB reports honoraria for lectures and educational events from Roche, AstraZeneca, and GSK; and support for attending meetings from Roche, AstraZeneca, and Viatris. AO reports consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for Gynecologic Cancer Intergroup and European Society for Medical Oncology; and other financial or non-financial interests in Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and GOG Foundation. EP reports provision of study material from MSD; honoraria for lectures, presentations, and educational events from MSD, Roche, GSK, and AstraZeneca; and receipt of investigational drug for study treatment from MSD. PL, KY, ST, and SMK are current or former full-time employees of MSD and hold stock or restricted stock units in the company. SP reports research funding from Roche, MSD, GSK, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, Roche, Pfizer, Novartis, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for GSK, MSD, Eisai, Biontech, and AstraZeneca. LRD reports institutional grants from Merck, Genentech, Roche, AbbVie, Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK, Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; royalties or licenses from UpToDate, Wiley, and ASCO; editing for ASCO Connection; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Advance Medical, CEA Group, and Clinical Care Options; participation on a data safety monitoring board for Innovia and Aegenus (payment to institution); and roles as Secretary Treasurer for SGO (unpaid) and on the Editorial Board of the British Journal of Obstetrics and Gynaecology., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Peri-implantitis, a plaque-associated pathological condition, has been on the rise with the increasing prevalence of dental implants. Despite its similarities to periodontitis, peri‑implantitis is difficult to control completely and has high relapse rates. This has sparked interest in exploring the pathogenic differences between the two conditions., Methods: This cross-sectional study involved 10 participants to concurrently examine periodontitis and peri‑implantitis within the same patients, thereby minimizing inter-individual variation. Gingival tissue samples were collected from each participant, comprising 10 periodontitis and 10 peri‑implantitis tissues, and RNAs were extracted. Using RNA sequencing and bioinformatics analysis, we investigated complex gene interactions, immune responses, and the role of the extracellular matrix in both conditions. We identified hub genes in each enhanced Protein-Protein Interaction network, providing crucial insights into these diseases' pathogenesis., Results: Our findings highlighted the potential involvement of activated fibroblasts in the pathogenesis of peri‑implantitis, identifying three marker genes (ACTA2, FAP, and PDGFRβ) overexpressed in peri‑implantitis, thus highlighting their potential as disease-specific biomarkers., Conclusions: Our study uncovered a novel connection between peri‑implantitis and activated fibroblasts, examining specific markers and microbial differences between periodontitis and peri‑implantitis. These insights improve our understanding of peri‑implantitis pathogenesis, encouraging future research for better management and prevention strategies., Clinical Significance: This study identifies key insights into the pathogenesis of peri‑implantitis compared to periodontitis. These findings promise to advance clinical approaches for better managing and preventing peri‑implantitis, addressing its complexities and high relapse rates effectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yun Hak Kim reports financial support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: The objective of this study was to investigate the efficacy of CRISPR/Cas9-mediated A4GALT suppression in rescuing endothelial dysfunction in Fabry disease (FD) endothelial cells (FD-ECs) derived from human induced pluripotent stem cells (hiPSCs)., Methods: We differentiated hiPSCs (WT (wild-type), WTC-11), GLA-mutant hiPSCs (GLA-KO, CMC-Fb-002), and CRISPR/Cas9-mediated A4GALT-KO hiPSCs (GLA/A4GALT-KO, Fb-002-A4GALT-KO) into ECs and compared FD phenotypes and endothelial dysfunction. We also analyzed the effect of A4GALT suppression on reactive oxygen species (ROS) formation and transcriptome profiles through RNA sequencing., Results: GLA-mutant hiPSC-ECs (GLA-KO and CMC-Fb-002) showed downregulated expression of EC markers and significantly reduced α-GalA expression with increased Gb-3 deposition and intra-lysosomal inclusion bodies. However, CRISPR/Cas9-mediated A4GALT suppression in GLA/A4GALT-KO and Fb-002-A4GALT-KO hiPSC-ECs increased expression levels of EC markers and rescued these FD phenotypes. GLA-mutant hiPSC-ECs failed to form tube-like structure in tube formation assays, showing significantly decreased migration of cells into the scratched wound area. In contrast, A4GALT suppression improved tube formation and cell migration capacity. Western blot analysis revealed that MAPK and AKT phosphorylation levels were downregulated while SOD and catalase were upregulated in GLA-KO hiPSC-ECs. However, suppression of A4GALT restored these protein alterations. RNA sequencing analysis demonstrated significant transcriptome changes in GLA-mutant EC, especially in angiogenesis, cell death, and cellular response to oxidative stress. However, these were effectively restored in GLA/A4GALT-KO hiPSC-ECs., Conclusions: CRISPR/Cas9-mediated A4GALT suppression rescued FD phenotype and endothelial dysfunction in GLA-mutant hiPSC-ECs, presenting a potential therapeutic approach for FD-vasculopathy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Automatic tracking of viral and intracellular structures displayed as spots with varying sizes in fluorescence microscopy images is an important task to quantify cellular processes. We propose a novel probabilistic tracking approach for multiple particle tracking based on multi-detector and multi-scale data fusion as well as Bayesian smoothing. The approach integrates results from multiple detectors using a novel intensity-based covariance intersection method which takes into account information about the image intensities, positions, and uncertainties. The method ensures a consistent estimate of multiple fused particle detections and does not require an optimization step. Our probabilistic tracking approach performs data fusion of detections from classical and deep learning methods as well as exploits single-scale and multi-scale detections. In addition, we use Bayesian smoothing to fuse information of predictions from both past and future time points. We evaluated our approach using image data of the Particle Tracking Challenge and achieved state-of-the-art results or outperformed previous methods. Our method was also assessed on challenging live cell fluorescence microscopy image data of viral and cellular proteins expressed in hepatitis C virus-infected cells and chromatin structures in non-infected cells, acquired at different spatial-temporal resolutions. We found that the proposed approach outperforms existing methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We generated a human induced pluripotent stem cell (hiPSC) line (CMCi014-A-78) expressing a GFP reporter in the 3'-UTR region of the KLOTHO locus using CRISPR/Cas9-mediated homologous recombination to screen for candidates regulating KLOTHO. The established cell line exhibits a normal karyotype, typical stem cell morphology, expression of pluripotency markers, and the ability to differentiate into the three germ layers. Consequently, this hiPSC line could serve as a valuable resource for screening KLOTHO regulators in hiPSC-derived target cells or organoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Accurate estimation of cell viability is crucial in various applications such as cytotoxicity testing and routine cell culture on both industrial and laboratory scales. For this, the real-time monitoring of cell status would be beneficial. Conventional cell-based assays for cell viability have limitations in sensitivity and time-effectiveness. Analysis of cell-free DNA (cfDNA) in (culture) media is a good alternative as cfDNA release are a well-known phenomenon during cell death., Results: We demonstrate a direct digital PCR (dPCR) method to estimate cell viability by analyzing cfDNA in media during induced cell death. After validating the duplex dPCR method for short and long amplicons of the SMAD4 and RPP30 loci, we determined that a media volume of 2 μL is feasible to measure the target DNA copy number with minimal negative effects on amplification. dPCR inhibition was evident with a higher media volume per reaction targeting long amplicons. Next, we applied our dPCR method using media cfDNA and other conventional methods to the monitoring of camptothecin (CPT)-induced cell death. Copy numbers increased significantly after 4 h of CPT treatment, showing a fold change of approximately 4-6 compared to the controls. Cell-based assays such as the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and annexin V/7-AAD assay also indicated increased cell death at 4 h, but the trypan blue exclusion assay did not., Significance: The developed media cfDNA direct dPCR method allows for efficient measurements of the degree of cell viability. Unlike other conventional cell-based assays, our method has advantages of no loss of cultured cells and the ability to implement online analysis. Accurate and sensitive media cfDNA analysis using dPCR can be adopted in various applications such as determining cytotoxicity levels in large-scale bioreactors or screening for effective anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year., Methods: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed., Findings: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups., Interpretation: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions., Funding: Abbott Vascular and Cardiovascular Research Center., Translation: For the Korean translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests S-JH reports speaker fees from AstraZeneca, Amgen, ChongKunDang, Hanmi, and Viatris; and participation on the data safety monitoring board of the IVUS-DCB trial. S-JL reports research grants and speaker fees from Boston Scientific, Medtronic, ChongKunDang, and Sam Jin Pharmaceutical. JHH reports consulting and speaker fees from Abbott Vascular. J-WL reports consulting fees from Genoss; speaker fees from Yuhan, Boryoung, Sam Jin Pharmaceutical, ChongKunDang, Korea United Pharm, HK inno.N, Novartis, Boehringer Ingelheim, AstraZeneca, Medtronic, Abbott Vascular, Amgen, Sanofi, Boston Scientific, Daiichi-Sankyo, Daewoong Pharmaceutical, Biosensors, Dong-A ST, and JW Pharmaceutical; and participation on the data safety monitoring board of the Rescue-SHOCK trial. J-SK reports grants from Sam Jin Pharmaceutical, Yuhan, Daiichi-Sankyo, Biosensors, and Qualitech Korea and proctoring fees from Abbott Vascular. Y-GK reports research grants from Medtronic, Korea United Pharm, Cook Medical, Boston Scientific, Otsuka Korea, Dong-A ST, Sam Jin Pharmaceutical, Cordis, HK inno.N, and GC Biopharma. M-KH reports research grants, paid to their institution, from Sam Jin Pharmaceutical and ChongKunDang and honoraria for lectures from Medtronic and Edwards Lifesciences. YJ reports research grants, paid to their institution, from Abbott Vascular. B-KK reports research grants and speaker or consulting fees from Abbott Vascular, Yuhan, Sam Jin Pharmaceutical, ChongKunDang, Medtronic, Boston Scientific, Biotronik, Genoss, CGBIO, MicroPort, Daewoong Pharmaceutical, Amgen, Bayer Korea, DIO Medical, Hanmi, AstraZeneca, and Novartis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Angiosarcoma is a rare endothelial-derived malignancy that is extremely diverse in anatomy, aetiology, molecular and immune characteristics. While novel therapeutic approaches incorporating targeted agents and immunotherapy have yielded significant improvements in patient outcomes across several cancers, their impact on angiosarcoma remains modest. Contributed by its heterogeneous nature, there is currently a lack of novel drug targets in this disease entity and no reliable biomarkers that predict response to conventional treatment. This review aims to examine the molecular and immune landscape of angiosarcoma in association with its aetiology, anatomical sites, prognosis and therapeutic options. We summarise current efforts to characterise angiosarcoma subtypes based on molecular and immune profiling. Finally, we highlight promising technologies such as single-cell spatial "omics" that may further our understanding of angiosarcoma and propose strategies that can be similarly applied for the study of other rare cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Evidence for the long-term use of antiplatelet drugs to prevent hepatic vascular complications (HVC) is scarce in liver transplantation (LT)., Methods: From national claim data, LT recipients (about 80 % of living donor LT [LDLT]) without graft loss, HVC, or cardiovascular events within 1 year, were classified into those who took antiplatelets for ≥1 year (n = 1744) and for <1 year (n = 1975). Outcomes were compared after the 1-postoperative year index time point., Results: During a mean follow up of 4.5 years, the risk of graft loss was similar between the groups (aHR 1.16, P = 0.23). However, ≥1-year antiplatelet therapy was associated with a higher risk of graft loss after 3 years (aHR 2.19, P < 0.01). HVC (aHR 0.94, P = 0.87) and major adverse cardiac events (aHR 1.20, P = 0.46) did not correlate with antiplatelet therapy for both groups. In contrast, ≥1-year antiplatelet therapy showed a significantly higher risk of severe bleeding compared to <1-year antiplatelet therapy (aHR 2.24, P < 0.01). This trend was similar in the LDLT subgroup. In our cohort, antiplatelet therapy for ≥1 year did not improve graft survival or HVC; however, it increased the risk of severe bleeding., Conclusion: We recommend against antiplatelet therapy for more than 1 year in clinically stable LT recipients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Implantable bioelectrodes have attracted significant attention for precise in vivo signal transduction with living systems. Conductive polymers, including polypyrrole (PPy), have been widely used as bioelectrodes due to their large surface areas, high charge injections, and versatilities for modification. Especially, several natural biopolymers, such as hyaluronic acid (HA), can be incorporated into conductive polymers to produce biomimetic electrodes with better biocompatibility. However, HA-incorporated PPy electrodes (PPy/HA) frequently lose their original performances after implantation in the body because of the deterioration of material properties, such as degradation of natural biopolymers in the electrode. Here, thiolated HA (HA-SH) was synthesized and introduced into PPy electrodes (PPy/HA-SH) to enhance the enzymatic stabilities of PPy electrodes against hyaluronidase (HAase) and endow these electrodes with robust resistances to non-specific cell adhesion, thereby enabling prolonged signal transmission. Unlike PPy/HA, PPy/HA-SH resisted cell adhesion even in the presence of HAase. Subcutaneous implantation studies revealed that PPy/HA-SH formed less fibrotic scar tissue and permitted more sensitive and stable signal recording for up to 15 days after implantation as compared to PPy/HA. These findings hold significance for the design and advancement of biocompatible implantable bioelectrodes for a wide range of applications, such as neural electrodes, cardiac pacemakers, and biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Quantitative bias analysis (QBA) methods evaluate the impact of biases arising from systematic errors on observational study results. This systematic review aimed to summarize the range and characteristics of QBA methods for summary-level data published in the peer-reviewed literature., Study Design and Setting: We searched MEDLINE, Embase, Scopus, and Web of Science for English-language articles describing QBA methods. For each QBA method, we recorded key characteristics, including applicable study designs, bias(es) addressed; bias parameters, and publicly available software. The study protocol was preregistered on the Open Science Framework (https://osf.io/ue6vm/)., Results: Our search identified 10,249 records, of which 53 were articles describing 57 QBA methods for summary-level data. Of the 57 QBA methods, 53 (93%) were explicitly designed for observational studies, and 4 (7%) for meta-analyses. There were 29 (51%) QBA methods that addressed unmeasured confounding, 19 (33%) misclassification bias, 6 (11%) selection bias, and 3 (5%) multiple biases. Thirty-eight (67%) QBA methods were designed to generate bias-adjusted effect estimates and 18 (32%) were designed to describe how bias could explain away observed findings. Twenty-two (39%) articles provided code or online tools to implement the QBA methods., Conclusion: In this systematic review, we identified a total of 57 QBA methods for summary-level epidemiologic data published in the peer-reviewed literature. Future investigators can use this systematic review to identify different QBA methods for summary-level epidemiologic data., Plain Language Summary: Quantitative bias analysis (QBA) methods can be used to evaluate the impact of biases on observational study results. However, little is known about the full range and characteristics of available methods in the peer-reviewed literature that can be used to conduct QBA using information reported in manuscripts and other publicly available sources without requiring the raw data from a study. In this systematic review, we identified 57 QBA methods for summary-level data from observational studies. Overall, there were 29 methods that addressed unmeasured confounding, 19 that addressed misclassification bias, six that addressed selection bias, and three that addressed multiple biases. This systematic review may help future investigators identify different QBA methods for summary-level data., Competing Interests: Declaration of competing interest In the past 36 months, T.L.L. served as a member of the Amgen Methods Advisory Council, for which he received consulting fees and travel support. J.S.R. reported receiving grants from the US Food and Drug Administration; Johnson and Johnson; Medical Device Innovation Consortium; Agency for Healthcare Research and Quality; National Heart, Lung, and Blood Institute; and Arnold Ventures outside the submitted work and is also is an expert witness at the request of relator attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled in September 2022. M.M.J reported receiving grants from the US Food and Drug Administration; Agency for Healthcare Research and Quality; National Heart, Lung, and Blood Institute; National Center for Advancing Translational Sciences; National Institute on Drug Abuse; and American Cancer Society. J.D.W. is supported by Arnold Ventures, Johnson & Johnson through the Yale Open Data Access project, and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award 1K01AA028258 and previously served as a consultant to Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pharmaceuticals, personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have seen a recent sustained increase in usage, leading to increasing discharge and accumulation in wastewater. Conventional water treatment and disinfection processes are somewhat limited in effectively addressing this micropollutant issue. Ultrasonication (US), which serves as an advanced oxidation process, is based on the principle of ultrasound irradiation, exposing water to high-frequency waves, inducing thermal decomposition of H 2 O while using the produced radicals to oxidize and break down dissolved contaminants. This review evaluates research over the past five years on US-based technologies for the effective degradation of EDCs and PPCPs in water and assesses various factors that can influence the removal rate: solution pH, temperature of water, presence of background common ions, natural organic matter, species that serve as promoters and scavengers, and variations in US conditions (e.g., frequency, power density, and reaction type). This review also discusses various types of carbon/non-carbon catalysts, O 3 and ultraviolet processes that can further enhance the degradation efficiency of EDCs and PPCPs in combination with US processes. Furthermore, numerous types of EDCs and PPCPs and recent research trends for these organic contaminants are considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Colorectal cancer is one of the most common cancers in the world. While colonoscopy is an effective screening technique, navigating an endoscope through the colon to detect polyps is challenging. A 3D map of the observed surfaces could enhance the identification of unscreened colon tissue and serve as a training platform. However, reconstructing the colon from video footage remains difficult. Learning-based approaches hold promise as robust alternatives, but necessitate extensive datasets. Establishing a benchmark dataset, the 2022 EndoVis sub-challenge SimCol3D aimed to facilitate data-driven depth and pose prediction during colonoscopy. The challenge was hosted as part of MICCAI 2022 in Singapore. Six teams from around the world and representatives from academia and industry participated in the three sub-challenges: synthetic depth prediction, synthetic pose prediction, and real pose prediction. This paper describes the challenge, the submitted methods, and their results. We show that depth prediction from synthetic colonoscopy images is robustly solvable, while pose estimation remains an open research question., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Danail Stoyanov reports financial support was provided by Medtronic plc. Danail Stoyanov reports a relationship with Odin Medical Ltd. that includes: equity or stocks. Laurence Lovat and Rawen Kader report a relationship with Olympus Corporation that includes: consulting or advisory., (Copyright © 2024. Published by Elsevier B.V.)

Plasticizers are necessary for the usability of various products, including food contact materials. Exposure to plasticizers is most commonly made through the oral route. Several plasticizers have been reported to have adverse effects on humans and the environment. Thus, the present study aimed to determine the long-term toxicity and carcinogenicity of a novel plasticizer called bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), which is an ecofriendly and biologically less harmful replacer. Groups of 50 male and 50 female Han Wistar rats were fed Eco-DEHCH at daily doses of 1,600, 5,000, or 16,000 ppm in their diet for at least 104 weeks. The rats were regularly monitored for mortality, clinical signs, body weight, food consumption, food efficiency, and perceivable mass. All animals were subjected to complete necropsy and histopathological examination. The results indicate that the rats well tolerated chronic exposure to Eco-DEHCH at highest daily doses of 16,000 ppm, with was equivalent to 805.1 mg/kg/day in males and 1060.6 mg/kg/day in females and did not show signs of toxicity or carcinogenicity. In conclusion, Eco-DEHCH could be a safe and promising alternative plasticizer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Polyhydroxyalkanoates (PHAs) are natural biopolyesters produced by microorganisms that represent one of the most promising candidates for the replacement of conventional plastics due to their complete biodegradability and advantageous material properties which can be modulated by varying their monomer composition. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] has received particular research attention because it can be synthesized based on the same microbial platform developed for poly(3-hydroxybutyrate) [P(3HB)] without much modification, with as high productivity as P(3HB). It also offers more useful mechanical and thermal properties than P(3HB), which broaden its application as a biocompatible and biodegradable polyester. However, a significant commercial disadvantage of P(3HB-co-3HV) is its rather high production cost, thus many studies have investigated the economical synthesis of P(3HB-co-3HV) from structurally related and unrelated carbon sources in both wild-type and recombinant microbial strains. A large number of metabolic engineering strategies have also been proposed to tune the monomer composition of P(3HB-co-3HV) and thus its material properties. In this review, recent metabolic engineering strategies designed for enhanced production of P(3HB-co-3HV) are discussed, along with their current status, limitations, and future perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although silicate fertilizer has been recently recognized for its ability to suppress methane (CH 4 ) emissions in paddy fields, the effects of its consecutive application during the rice farming period are still a subject of debate. Moreover, while it was known that silicate fertilizer can mitigate CH 4 emissions through several electron acceptors, the effect of additional application of electron acceptors have not been extensively studied. This study evaluated the effect of silicate fertilizer with varying concentrations of iron slag on CH 4 emissions and rice yield over the 3 years rice farming period. Seasonal CH 4 fluxes exhibited a significant decrease with the application of silicate fertilizer, with the treatment containing 2.5 % iron slag showing the maximum reduction of 35 % in 2020. Additionally, in 2021 and 2022, the application of silicate fertilizer with 2.5 % iron slag resulted in a decrease of total seasonal CH 4 emission by 22 % and 23 %, respectively. Rice grain yield exhibited a significant increase with the inclusion of iron slag in the silicate fertilizer, which resulted in a 37 % and 16 % higher yield compared to no-silicate fertilization and no‑iron slag silicate fertilization, respectively. Therefore, iron slag-based silicate fertilizer could be a beneficial soil amendment to mitigate CH 4 emissions in rice paddy fields and improve rice productivity without negative effects on the atmospheric and soil ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment., Participants: VigiBase, a World Health Organization (WHO) global safety report database., Design: Pharmacovigilance study., Methods: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database)., Main Outcome Measures: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC 025 ) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR)., Results: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC 025 0.75; ROR: 1.78 [95% CI, 1.70-1.86]), angina pectoris (IC 025 0.53; ROR: 1.61 [95% CI, 1.47-1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC 025 > 0 , .ROR>1), hypertension (IC 025 2.22; ROR: 4.91 [95% CI, 4.82-5.01]), and hypertensive crisis (IC 025 1.97; ROR: 4.49 [95% CI, 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC 025 4.34; ROR: 23.19 [95% CI, 22.10-24.34]), carotid artery stenosis (IC 025 1.85; ROR: 5.24 [95% CI, 3.98-6.89]), cerebral hemorrhage (IC 025 2.29; ROR: 5.38 [95% CI, 5.03-5.76]), and subarachnoid hemorrhage (IC 025 1.98; ROR: 4.81 [95% CI, 4.14-5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40-0.65])., Conclusions: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. Although ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Height loss in aging has been recognized to reflect a decline in musculoskeletal health but not investigated in relation to dietary factors, such as sugar-sweetened beverages (SSBs), the consumption of which may deteriorate musculoskeletal health., Objectives: This study aimed to evaluate the longitudinal association of habitual consumption of total SSBs and its subtypes with height loss and examine effect-modification by age, sex, and anthropometry., Methods: We evaluated 16,230 adults aged 40-79 y in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. At baseline (1993-1997), SSB consumption (soft drinks, squashes, sweetened milk beverages, sweetened coffee/tea, and sweetened alcoholic beverages) was assessed using 7-d food diaries. Height was objectively measured at the baseline, second (1997-2000), and third (2004-2011) health checks. Multivariable linear regression was used to examine baseline SSB consumption and the rate of height change over the follow-up., Results: The median (IQR) height change was -1.07 (-2.09 to -0.28) cm/10 y. Adjusted for potential confounders including behavioral factors, medications, and baseline body mass index (BMI), total SSB consumption was associated with height loss (β: -0.024; 95% CI: -0.046, -0.001 cm/10 y per 250 g/d of SSB), and similar results were seen for the individual beverages, except for sweetened milk beverages (β: +0.07; 95% CI: -0.16, 0.30), with wide CIs. No effect-modification by prespecified factors was evident, except for baseline BMI (P-interaction = 0.037). Total SSB consumption was associated with height loss (-0.038; 95% CI: -0.073, -0.004) in participants with BMI ≤ 25 kg/m 2 but not apparently in those with BMI > 25 kg/m 2 ., Conclusions: SSB consumption was modestly associated with height loss, particularly in adults with normal weight status., (Copyright © 2024. Published by Elsevier Inc.)

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria., Competing Interests: Disclosure Statement T.J.O., Y.S., M.A.W., and S.A. are employees and shareholders of Genomictree, Inc.; B.-R.B., C.S.I., S.K., J.J.L., S.B., and S.A. are employees of Promis Diagnostics, Inc.; and J.J.L. and S.A. are shareholders of Promis Diagnostics Inc., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. All rights reserved.)

Purpose: Proper breast cancer screening and treatment should be considered in the elderly population; however, some tend to be less proactive. Our study aimed to investigate the impact of old age on treatment and prognosis in triple-negative breast cancer (TNBC)., Method: The study included patients with primary TNBC stage I-III diagnosed from 2002 to 2019 in single institution and retrospectively analyzed. We defined young (< 40 years), middle and old (> 70 years) groups. Clinicopathological factors, treatment, and prognosis were analyzed according to age group of TNBC patients., Result: TNBC patients aged 70 and above were 3.3 times more likely (P = .019) to have lymph node metastasis at the time of diagnosis compared to younger patients, but were found to be 0.24 times less likely to receive chemotherapy. (P = .003) Old TNBC patients have an expected likelihood 2.2 times higher of undergoing mastectomy rather than breast-conserving surgery. (P = .042) The 5-year prognosis is poorer in young and old group. (61%, 86%, and 65% in young, middle, and old groups). (P < .001). In subanalysis, old group of stages I and II received fewer chemotherapy compared to youngers (P < .05), but not in stage III. In Cox regression analysis, age and stage had significant impact on prognosis (hazard ratio 2-3), but treatment factors did not. However, in stratified analysis of adjuvant therapy and stage, prognosis of Old TNBC patients in stage II was improved when they underwent neo or adjuvant chemotherapy., Conclusion: TNBC presents challenges in older patients, who receive less aggressive treatment and have poorer outcomes. The primary cause of poor prognosis in old TNBC patients is the high disease stage at diagnosis, underscoring the need for promotion and education on early screening. Additionally, it is suggested that a more proactive approach to adjuvant chemotherapy is necessary for stage II old TNBC patients., Competing Interests: Disclosure The authors have no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tooth autotransplantation (AT) involves the surgical relocation of a tooth from 1 site in the mouth to another site within the same patient. This approach is a good option in a growing patient when dental implant placements or fixed bridges are not suitable and when preserving natural teeth is a priority. Tooth AT is a complex procedure that requires specialized skills from a multidisciplinary team with careful patient and tooth selection and treatment planning., Types of Studies Reviewed: The authors provided a review of the state of knowledge and research on tooth AT and presented a case scenario and barriers to adoption, with a focus on the United States., Results: Success rates for tooth AT can vary depending on several factors, including the patient's overall health, specific tooth involved, skill of the dental surgeon, and postoperative care provided. Long-term outcomes of autotransplanted teeth have been cited in the literature with impressive longitudinal follow-up spanning up to 26 years. Results of several systematic reviews showed survival rates from 75% through 98%., Conclusions and Practical Implications: Adoption of tooth AT has grown over the years, owing to advancements in dental techniques, improved patient outcomes, and increased awareness among both dentists and patients. Increasing awareness and availability of tooth AT to replace missing teeth can provide a natural and functional alternative to traditional prosthetic options. Tooth AT helps preserve the alveolar bone in growing patients and can offer excellent esthetic and functional outcomes., Competing Interests: Disclosure None of the authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI)., Objectives: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation., Methods: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization., Results: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69)., Conclusions: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872)., Competing Interests: Funding Support and Author Disclosures This trial is investigator initiated with grant support from Abbott Vascular and Boston Scientific. The sponsors were not involved with the protocol development or study process, including site selection, management, data collection, or analysis of the results. Dr Chan Joon Kim has received research grants from Basic Science Research Program, National Research Foundation of Korea, Ministry of Education, Hanmi Pharmaceutical, Chong Keun Dang Pharm, Handoc Kalos Medical, Donga-ST, and Boryung Corporation. Dr Joo Myung Lee has received institutional research grants from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Zoll Medical, and Donga-ST. Dr Hyeon-Cheol Gwon has received institutional research grants from Abbott Vascular, Boston Scientific, and Medtronic Inc. Dr Joo-Yong Hahn has received institutional research grants from the National Evidence-based Healthcare Collaborating Agency, Ministry of Health and Welfare (Korea), Abbott Vascular, Biosensors, Boston Scientific, Daiichi-Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP 2 ) into phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest. The funders had no role in the design of the study; collection, analyses, or interpretation of data; writing of the manuscript, or decision to publish the results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The hygroscopicity of PM 2.5 particles plays an important role in PM 2.5 haze in Northeast Asian countries by influencing particle growth and chemical composition. New particle formation (NPF) and atmospheric volatile organic compounds (VOCs) are factors that influence particle hygroscopicity. However, the lack of real-time hygroscopicity measurements has deterred the understanding of their effects on particle hygroscopicity. In this study, two intensive monitoring campaigns were conducted during the summer of 2021 and spring of 2022 using real-time aerosol instruments, including a humidified tandem differential mobility analyzer (HTDMA), in Seosan, Republic of Korea. The hygroscopicity parameter κ was calculated from the real-time HTDMA measurement data (κ Gf ). The diurnal variations in κ Gf exhibited strong inverse linear correlations with the total concentration of VOCs (C TVOC ) during the two campaigns. The higher atmospheric C TVOC in summer increased the growth rate of the particle diameter from 10 to 40 nm (6 nm/h) compared with that in spring (2.7 nm/h), resulting in a faster change in κ Gf for 40-nm particles in summer than in spring because of the increase in organic matter in the chemical compositions of particles. In addition, NPF events introduced additional tiny fresh particles into the atmosphere, which reduced the κ Gf of 40-nm particles and increased the intensity of the less hygroscopic peaks (κ Gf  < 0.1) of κ-probability density functions (κ-PDF) in NPF days. However, 100-nm particles exhibited fewer changes in κ Gf than 40-nm particles, resulting in additional dominant hygroscopic peaks (κ ∼ 0.2) of κ-PDFs in both NPF and non-NPF days. When κ Gf values measured in Seosan were compared with those in other Northeast Asian countries in the literature, the κ values for 40-nm particles were lower than those (κ > 0.2) measured in Beijing and Guangzhou, but those for 100-nm particles were close to those measured in the two cities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic inflammation, generalized lymphadenopathy, and organ dysfunction. Here, we present an unusual occurrence of iMCD in identical twins and examined the immune milieu within the affected lymphoid organs and the host circulation using multiomic high-dimensional profiling. Using spatial enhanced resolution omics sequencing (Stereo-seq) transcriptomic profiling, we performed unsupervised spatially constrained clustering to identify different anatomic structures, mapping the follicles and interfollicular regions. After a cell segmentation approach, interleukin 6 (IL-6) pathway genes significantly colocalized with endothelial cells and fibroblastic reticular cells, confirming observations using a single-cell sequencing approach (10× Chromium). Furthermore, single-cell sequencing of peripheral blood mononuclear cells revealed an "inflammatory" peripheral monocytosis enriched for the expression of S100A family genes in both twins. In summary, we provided evidence of the putative cell-of-origin of IL-6 signals in iMCD and described a distinct monocytic host immune response phenotype through a unique identical twin model., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Seoul has high PM 2.5 concentrations and has not attained the national annual average standard so far. To understand the reasons, we analyzed long-term (2015-2021) hourly observations of aerosols (PM 2.5 , NO 3 - , NH 4 + , SO 4 2- , OC, and EC) and gases (CO, NO 2 , and SO 2 ) from Seoul and Baekryeong Island, a background site in the upwind region of Seoul. We applied the weather normalization method for meteorological conditions and a 3-dimensional chemical transport model, GEOS-Chem, to identify the effect of policy implementation and aerosol formation mechanisms. The monthly mean PM 2.5 ranges between about 20 μg m -3 (warm season) and about 40 μg m -3 (cold season) at both sites, but the annual decreasing rates were larger at Seoul than at Baengnyeong (-0.7 μg m -3 a -1 vs. -1.8 μg m -3 a -1 ) demonstrating the effectiveness of the local air quality policies including the Special Act on Air Quality in the Seoul Metropolitan Area (SAAQ-SMA) and the seasonal control measures. The weather-normalized monthly mean data shows the highest PM 2.5 concentration in March and the lowest concentration in August throughout the 7 years with NO 3 - accounting for about 40 % of the difference between the two months at both sites. Taking together with the GEOS-Chem model results, which reproduced the elevated NO 3 - in March, we concluded the elevated atmospheric oxidant level increases in HNO 3 (which is not available from the observation) and the still low temperatures in March promote rapid production of NO 3 - . We used O x (≡ O 3  + NO 2 ) from the observation and OH from the GEOS-Chem as a proxy for the atmospheric oxidant level which can be a source of uncertainty. Thus, direct observations of OH and HNO 3 are needed to provide convincing evidence. This study shows that reducing HNO 3 levels through atmospheric oxidant level control in the cold season can be effective in PM 2.5 mitigation in Seoul., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ibuprofen, one of the most commonly prescribed nonsteroidal anti-inflammatory drugs, has not been fully assessed for embryonic toxicity in vertebrates. Here, we systematically assessed the embryotoxicity of ibuprofen in Xenopus laevis at various concentrations during embryogenesis. Embryos were treated with different concentrations of ibuprofen, ranging from 8 to 64 mg/L, at 23 °C for 96 h, and examined daily and evaluated at 72 hpf. Lethal or teratogenic effects were documented. For histological analysis, paraffin embedded embryos were transversely sectioned at a thickness of 10-μm and stained with hematoxylin and eosin. Total RNA was isolated from embryos at stages 6, 12, 22 and 36, and real-time quantitative PCR was performed. Ibuprofen-treated embryos showed delayed or failed dorsal lip formation and its closure at the beginning of gastrulation. This resulted in herniation of the endodermal mass after gastrulation under high concentrations of ibuprofen-treated embryos. Underdeveloped intestines with stage and/or intestinal malrotation, distorted microcephaly, and hypoplastic heart, lungs, and pronephric tubules were observed in ibuprofen-treated embryos. Cephalic, cardiac, and truncal edema were also observed in them. The severity of the deformities was observed in a concentration-dependent manner. The teratogenic index was 2.28. These gross and histological disruptions correlated well with the altered expression of each organ marker gene. In conclusion, ibuprofen induced delayed and disrupted gastrulation in the early developmental stage and multiorgan malformation later in the organogenesis stage of Xenopus laevis embryos., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer., Methods: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD)., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AAc, VSu, NC, AJPdSG, FCM, AR, AAy, J-YL, VSa, FZ, LG, JS, ET, KLin, RLaz, C-LC, RLam, HZ, AO, MC, SPo, TU, SPi, and LRD received funding to their institutions from MSD to support the study. DL reports consulting fees from AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis, and PharmaMar; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, ImmunoGen, GSK, Seagen, and Genmab; support for attending meetings or travel from AstraZeneca, Clovis Oncology, and GSK; participation on a data safety monitoring board or advisory board for Oncoinvest, Corcept, Sutro, AstraZeneca, ImmunoGen, GSK, Seagen, Genmab, Clovis Oncology, GSK, MSD, and PharmaMar; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Clovis Oncology, GSK, MSD, and PharmaMar; and other financial or non-financial interests in AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Incyte, MSD, Roche, Seagen, and Novartis. YX reports participation on a data safety monitoring board or advisory board for MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, and Sanofi; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, and Kaken; and support for attending meetings or travel from Regeneron. GS reports grants or contracts from MSD Italia; consulting fees from Tesaro and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Clovis Oncology Italy. ML reports grants or contracts from MSD, AstraZeneca, and Roche; speaker fees from AstraZeneca and Roche; and meeting support from Roche. PR-E reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from MSD, Asofarma, Novartis, Janssen, and AstraZeneca; support for attending meetings or travel from Roche, Novartis, Asofarma, and AstraZeneca; and participation on a data safety monitoring board or advisory board for Pfizer, Asofarma, Bristol Myers Squibb, and AstraZeneca. NC reports participation on a data safety monitoring board or advisory board for GSK, Toray, Tarveda Therapeutics, Umoja, Kartos, Zentalis, Profound, and Novita Pharmaceuticals. AJPdSG reports consulting fees, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and participation on a data safety monitoring board or advisory board for AstraZeneca, Astellas, Bayer, and Janssen; payment for expert testimony from Janssen; and support for attending meetings or travel from Janssen, MSD, and Bayer. FCM reports speaker fees from MSD, Bristol Myers Squibb, GSK, Eli Lilly, and BMS; payment for expert testimony from MSD, Janssen, GSK, Eli Lilly, and Bristol Myers Squibb; and meeting and travel support from MSD and Amgen. AR reports advisory board fees from MSD Israel. J-YL reports grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, Bristol Myers Squibb, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, OncoQuest, Ono, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and Ono. FZ reports grants or contracts, consulting fees, payment for expert testimony, support for attending meetings or travel, participation on a data safety monitoring board or advisory board, and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, from AstraZeneca, Eli Lilly, MSD, Pfizer, Roche, Daiichi Sankyo, Merck, Novartis, Genesis Pharma, and Gilead. LG reports institutional grants from GSK, Pfizer, MSD, Karyopharm, Tesaro, IMV, Alkermes, Clovis Oncology, ImmunoGen, Roche, Mersana, and AstraZeneca; consulting fees from GSK, Merck, Eisai, and Novocure; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from GSK, Merck, Eisai, Novocure, and Corcept; and support for attending meetings or travel from Corcept, GSK, AstraZeneca, and Merck. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, Eisai, and Novartis; support for attending meetings or travel from GSK, AstraZeneca, Roche, Novocure, ImmunoGen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO. KLin reports grants or contracts from GSK (paid to institution); payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Eisai; and participation on a data safety monitoring board or advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK. HZ reports contracted research and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events for MSD. AO reports grants or contracts from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Roche, ImmunoGen, MSD de España, Millennium Pharmaceuticals, PharmaMar, Regeneron, and Tesaro (paid to institution); consulting fees and participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, Roche, Genmab, GSK, ImmunoGen, iTeos, MSD de España, Mersana, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen, and Sutro; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiana de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; and support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche. SPo reports consulting fees from MSD, AstraZeneca, GSK, and Eisai; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, support for attending meetings or travel, and advisory board fees from MSD, AstraZeneca, and GSK; and leadership or fiduciary role in other board, society, committee, or advocacy group for the Austrian Association of Gynecologic Oncology (unpaid). SPi reports research funding from Roche, MSD, AZ, Pfizer, and GSK; and honoraria from AZ, Roche, MSD, GSK, and PharmaMar. LRD reports research funding (paid to institution) from and acting as an expert advisor (unpaid) for Merck & Co; writing fees for expert content for UpToDate; participation on a scientific advisory board for Aadi Bioscience; and serving on the Editorial Board of the British Journal of Obstetrics and Gynaecology. KLi, KY, ST, and SMK are full-time employees of MSD and hold stock or restricted stock units in the company., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments., Objective: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein., Methods: Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582)., Results: The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol., Conclusion: Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations., Competing Interests: Declaration of Competing Interest Ms. Lee JY was an employee of Twi Biotechnology., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Combinations of semiconductor metal oxide (SMO) sensors, electrochemical (EC) sensors, and photoionization detection (PID) sensors were used to discriminate chemical hazards on the basis of machine learning. Sensing data inputs were exploited in the form of either numerical or image data formats, and the classification of chemical hazards with high accuracy was achieved in both cases. Even a small amount of gas sensing or purging data (input for ∼30 s) input can be exploited in machine-learning-based gas discrimination. SMO sensors exhibit high performance even in a single-sensor mode, presumably because of the intrinsic cross-sensitivity of metal oxides, which is otherwise considered a major disadvantage of SMO sensors. EC sensors were enhanced through synergistic integration of sensor combinations with machine learning. For precision detection of multiple target analytes, a minimum number of sensors can be proposed for gas detection/discrimination by combining sensors with dissimilar operating principles. The Type I hybrid sensor combines one SMO sensor, one EC sensor, and one PID sensor and is used to identify NH 3 gas mixed with sulfur compounds in simulations of NH 3 gas leak accidents in chemical plants. The portable remote sensing module made with a Type I hybrid sensor and LTE module can identify mixed NH 3 gas with a detection time of 60 s, demonstrating the potential of the proposed system to quickly respond to hazardous gas leak accidents and prevent additional damage to the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rice starch is a promising biopolymer for buccal formulations but typical oven drying may promote starch retrogradation that affects mechanical properties. Hence, lyophilisation was proposed here to improve starch product's stability. This study aims to investigate the effects of plasticisers (sorbitol and Tween® 80, T80) on the characteristics and drug release profiles of lyophilised rice starch wafers incorporated with propranolol hydrochloride. The wafers were prepared by lyophilising starch mixture (5%w/v) with plasticiser (0.2 and 0.3 g/g) and drug (10, 20, 30%w/w). Control wafers exhibited loose layers with rough wrinkled surface. Sorbitol resulted in a dense structure with higher puncture strength (PS) but lower water absorption capacity (WAC) while T80 loosened the flakes that reduced PS and increased WAC. Drug inclusion decreased PS and increased WAC of unplasticised wafers. T80-plasticised wafers with drug had a lower PS and higher WAC than sorbitol-plasticised wafers. Particularly, T80-plasticised wafers achieved outstandingly high PS and the lowest WAC at 30%w/w drug. Drug dissolution of wafers relied mainly on the drug crystallinity and WAC at 10 and 30%w/w drug. Plasticisers reduced and increased drug dissolution at 10 and 20%w/w drug, respectively. This study highlights the potential of lyophilisation in preparing rice starch wafers for buccal delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM 2.5 ) with the risk of KD., Methods: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM 2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders., Results: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM 2.5 exposed to the entire cohort was 28.2 μg/m³ (Standard Deviation 2.9). For each 5 μg/m³ increase in annual PM 2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39)., Conclusions: In this nationwide, population-based, cohort study, long-term childhood exposure to PM 2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM 2.5 and KD, but further studies are needed to confirm our findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Although injuries are a leading cause of death and affect the life expectancy of individuals who live with disabilities globally, the potential role of air pollution exposure on injuries due to external causes has received little scientific attention, especially compared with that given to the association of air pollution and non-external causes of morbidity and mortality. We investigated the association between emergency department visits for externally caused injuries and short-term exposure to major ambient air pollutants, with focus on the intentions and mechanisms of injuries. We identified 2,049,855 injured patients in Seoul, South Korea between 2008 and 2016 using the National Emergency Database. Daily short-term exposure to air pollution including particles <10 μm (PM 10 ) and <2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), carbon monoxide (CO), and ozone (O 3 ) was estimated based on hourly concentrations. We employed a time-stratified case-crossover study design using a conditional Poisson regression model adjusted for meteorological variables, influenza epidemics, and holidays. Immediate exposure (lag 0) to most pollutants significantly increased the risk of total injuries (PM 2.5 , 0.42 %; NO 2 , 0.68 %; SO 2 , 1.05 %; CO, 0.57 %; O 3 , 1.86 % per interquartile range increment), and the associations differed according to the intention and mechanism of injury. Unintentional and assault injuries were significantly associated with air pollution exposure, whereas self-harm injuries showed no association. In mechanism-specific analyses, injuries caused by falls, blunt objects, penetration, traffic accidents, machinery, and slips were associated with specific air pollutants, even in the co-pollutant models. The associations were stronger in injured patients aged <15 years, and in males than in their counterparts. Our results suggest that short-term air pollution exposure might play a role in the risk of externally caused injuries and the association may differ depending on the intention and mechanism of injury, which provide important evidence for injury prevention and air quality strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a group of illnesses associated with unresolved inflammation in response to toxic environmental stimuli. Persistent exposure to PM is a major risk factor for COPD, but the underlying mechanism remains unclear. Using our established mouse model of PM-induced COPD, we find that repeated PM exposure provokes macrophage-centered chronic inflammation and COPD development. Mechanistically, chronic PM exposure induces transcriptional downregulation of HAAO, KMO, KYNU, and QPRT in macrophages, which are the enzymes of de novo NAD + synthesis pathway (kynurenine pathway; KP), via elevated chromatin binding of the CCCTC-binding factor (CTCF) near the transcriptional regulatory regions of the enzymes. Subsequent reduction of NAD + and SIRT1 function increases histone acetylation, resulting in elevated expression of pro-inflammatory genes in PM-exposed macrophages. Activation of SIRT1 by nutraceutical resveratrol mitigated PM-induced chronic inflammation and COPD development. In agreement, increased levels of histone acetylation and decreased expression of KP enzymes were observed in pulmonary macrophages of COPD patients. We newly provide an evidence that dysregulated NAD + metabolism and consecutive SIRT1 deficiency significantly contribute to the pathological activation of macrophages during PM-mediated COPD pathogenesis. Additionally, targeting PM-induced intertwined metabolic and epigenetic reprogramming in macrophages is an effective strategy for COPD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Groundwater serves various purposes worldwide, including agricultural, drinking, domestic, and industrial uses. In the Republic of Korea, groundwater is used primarily for agricultural purpose. Understanding the quality of groundwater is crucial because microplastics (MPs) can enter groundwater through agricultural activities and potentially pose harm to humans. Therefore, groundwater sampling plays a vital role in determining the presence of MPs. However, the optimal volume of groundwater sampling required for accurate MP assessment remains uncertain. This study examined the optimal sample size for collecting MPs from groundwater in the heavy agricultural area of the Haean Basin, Korea. Groundwater sampling and MP analyses were conducted during the wet and dry seasons of 2022. A total of 500 L of groundwater was continuously sampled in increments of 100 L to 500 L (100, 200, 300, 400, and 500 L). Additionally, we investigated the land use surrounding the sampling wells and the predominant types of plastics used in agriculture. To ensure reliable MP analysis, precautions were taken to minimize plastic contact during sampling, pretreatment, and μ-FTIR analysis. The concentration of MPs in groundwater ranged from 0.04 to 17.77 particles/L during the wet season and from 0 to 0.56 particles/L during the dry season. The highest concentration of MPs was observed at the first 100 L sample volume, with concentrations decreasing as the sampling volume increased. Fragmented particles accounted for 86.3 % during the wet season and 91.5 % during the dry season, whereas fibers constituted 13.7 and 8.5 %, respectively. MPs in the size range of 20-100 μm were predominant in both seasons. The polymers identified in both seasons were polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), and polyamide (PA). While some studies suggest that 500 L is the optimal sample volume for assessing MPs in groundwater, the findings of this study indicate that a larger sample volume may be necessary. This study was the first attempt to determine the optimum sample volume required to collect MPs from groundwater, emphasizing the importance of conducting further research to validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)